Cancer is an abnormal disease state in which uncontrolled proliferation of one or more cell populations interferes with normal biological function. The proliferative changes are usually accompanied by other changes in cellular properties, including reversion to a less organised state. Cancer cells are typically referred to as “transformed”. Transformed cells generally display several of the following properties: spherical morphology, expression of foetal antigens, growth-factor independence, lack of contact inhibition, anchorage-independence, and growth to high density. Cancer cells form tumours and are referred to as “primary” or “secondary” tumours. A primary tumour results in cancer cell growth in an organ in which the original transformed cell develops. A secondary tumour results from the escape of a cancer cell from a primary tumour and the establishment of a secondary tumour in another organ. The process is referred to as metastasis and this process may be aggressive, for example as in the case of hepatoma or lung cancer. Prostate cancer can be relatively harmless or extremely aggressive. Some prostate tumours are slow growing and cause few clinical symptoms. Aggressive prostate tumours spread rapidly to the lymph nodes and other organs, especially bone. It is known that the growth of prostate cancer can be inhibited by blocking the supply of male hormones such as testosterone. However, prostate cancers eventually develop and become independent of male sex hormones (i.e. they become androgen-independent prostate cancer cells). These cells are linked with aggressive, malignant prostate cancer. Only two species suffer from prostate cancer; dogs and humans.
Previous studies have identified minichromosome maintenance proteins (MCM) as key regulators in the cell cycling process of epithelial tissue (see WO99/21014 and Gonzalez et al; Nature Reviews/Cancer, Vol 5: pp 135-141, February 2005). MCMs were identified as useful biomarkers of “cell cycle state”, i.e. whether a cell is capable of proliferating rather than being quiescent or senescent. Expression of all 6 MCMs (MCM 2-7) is seen throughout all phases of the cell cycle and is down regulated following exit from the cell cycle into quiescence, differentiation or senescence. Androgen Receptor [AR] is a nuclear protein that binds the androgens testosterone and dihydrotestosterone. AR is a transcription factor and is involved controlling genes involved male sex determination. The cloning and sequencing of AR is disclosed in WO89/09791 which describes the expression of AR in prokaryotic and eukaryotic expression systems and its use in the development of monoclonal antibodies. The detection of PSA as a diagnostic test to detect prostate cancer is well established. PSA is a protease secreted by the cells of the prostate gland. The detection of PSA in a blood sample is considered to be indicative of prostate cancer in a subject. This has considerable problems associated with clearly identifying whether a subject requires further investigation. Some subjects that present with high serum levels of PSA are eventually found not to have disease. This causes both psychological stress and unnecessary physical investigation.
We disclose an assay that provides a reliable test for the detection of prostate cancer cells in an isolated cell sample from a biological sample and removes the current problems associated with the detection of prostate specific antigen in serum samples of male subjects.